After finding themselves in a fight with supporters of The Alliance in a place that fairly resembles a bar, Mal, Zoe and Jayne walk away with knowledge that a man named Niska might have a new job for them.
The crew of Serenity find a dead spaceship at drift and takes the only surviving crew member aboard. Then an Alliance ship comes along whose commander is looking for the two fugitives, Simon and River.
A girl named 'Saffron' sneaks aboard Serenity and claims that she is Mal's wife. What he and the crew don't know is that she is secretly working with a company to betray the crew of Serenity, so they can steal the ship, take it apart, and sell its pieces.
The crew arrive at a planet where the local town mistakenly honor Jayne as a hero for giving money to the poor a few years ago.
After the engine fails to run, the ship starts to run out of oxygen. As the crew abandon ship, the captain stays behind to see if any nearby vessel responds to their distress call. Under the conditions of the low oxygen levels, Mal has flashbacks relating to how he assembled his crew.
Badger contacts Serenity and tells them he wants the crew to help a local crimelord on the planet Persephone to transport some goods. All Mal have to do is find that warlord in a big ball he's attending that evening. Meanwhile, a young man named Atherton Wing hires Inara to be his date at a ball, the same ball Mal is attending that evening.
Simon is kidnapped by some villagers who desperately need a doctor. Back at Serenity, Book is severely injured and needs medical help. Unable to find Simon, Serenity takes off without him to find medical help... in an Alliance facility.
The ship heads to Ariel to drop off Inara for her yearly companion health check-up. Simon realizes River's condition is getting worse and decides to sneak her into an Alliance hospital in Ariel for a brain scan. Mal and the others agrees to help him with his plan, but also takes this opportunity to steal some valuable medical supplies in the hospital and sell it at the street market.
Niska finally gets his revenge on Mal when his men find him and Wash on a planet. Nothing would please Niska more than to see them suffer right in front of him. Back at Serenity, Zoe and the crew decide to mount a daring rescue to get their friends back.
A bounty hunter named 'Jubal Early' sneaks aboard Serenity, hoping to capture River for an enormous reward. He takes Simon captive, hoping he will lead him to River. The only problem is that they can't find River anywhere aboard the ship.
The crew of Serenity is eager to rid themselves of an easily traceable cargo they salvaged from a vessel adrift in space.
Mal and his crew discovers what Simon is hiding in his cargo - his sister River. Simon is only trying to hide her away from the Alliance. Mal realizes helping Simon hiding her can cause trouble for him and his crew. Meanwhile, the crew still have to finish conducting business with Patience, while trying to dodge a Reaver ship along the way.
The crew comes to the aid of a bordello when its madam, an old acquaintance of Inara's, asks for help after a gunslinger claims a prostitute's baby is his and he's taking it because his wife is barren.
Mal is shocked to discover his friend's new wife is Saffron (first seen in episode "Our Mrs. Reynolds"). She offers him a cut on the big-time scam she's planning.
Mal and Zoe receive a package that contains the body of their old war buddy, Tracey.